Alkoxy and aryloxy isothiocyanates are well-known versatile, organic intermediates which, by virtue of highly reactive multifunctionalities, can undergo a variety of condensation and cyclization reactions. For instance, Helibron et al, J. Chem. Soc. 1948, 1340, made use of the ready addition of alkoxycarbonyl isothiocyanate to .alpha.-aminonitrites in their synthesis related to penicillin and purines. Other useful organic syntheses based on alkoxy and aryloxy isocyanate are set forth by Esmail et al. Synthesis, 301, (1975).
Ethoxycarbonyl isothiocyanate was first prepared by R. E. Doran in 1896 by reacting lead thiocyanate with ethylchloroformate in boiling toluene with relatively poor yields; J. Chem. Soc. 69, 324 (1896). In 1908, Dixon and Taylor reported, J. Chem. Soc. 93, 684 (1908), that methylchloroformate, ethylchloroformate, benzylchloroformate, phenyl chloroformate and o- and p-tolylchloroformate, were reacted with potassium thiocyanate in boiling acetone to form the corresponding isothiocyanate.
One of the reasons for low yields in Dixon et al's method was confirmed by Takamizawa et al to be the simultaneous formation of an unreactive thiocyanate isomer. With ethylchloroformate, two isomers were obtained in about 30% yields while with butylchloroformate the yields were 34% for the isothiocyanate and 21% for the thiocyanate isomer. Yields of 31% for the isothiocyanate and 3.5% for the thiocyanate isomer were obtained with allylchloroformate, it being postulated that the formation of the two isomers were due to the existence of the mesomeric thiocyanate ion and isothiocyanate ion both of which can effect the nucleophilic attack on the carbonyl carbon and cause the thiocyanate and isothiocyanate isomer product. Later workers improved reaction conditions to favor the isothiocyanate formation by adding catalytic amounts of triethylamine and longer reaction times; Goerdeler et al, Chem Ber. 104, 1606 (1971). The use of acetonitrile and ethyl acetate as solvents was reported by Lamon; J. Heterocyclic Chem., 5, 837 (1968); Goerdeler et al; Chem. Ber. 96, 526, (1963). Yields, however, were only up to about 60%. Anders et al, Ger. Pat. No. 1215144, 1966, reported the preparation of alkoxy and aryloxy isothiocyanates using silyl isothiocyanate while Goerdeler et al, Chem. Ber. 98, 2954 (1965) disclosed the pyrolysis of thiozolinediones as a means for producing them, see also Schenk, Chem. Ber. 99, 1258 (1966).
In a later publication, Chem. Ber. 116, 2044, (1983), Goerdeler et al reported the use of an aromatic heterocyclic nitrogen catalyst such as pyridine in carbon tetrachloride for the preparation of alkoxythiocarbonyl isothiocyanate, however, the yield was only 52%. Using the propoxyanalog, Goerdeler et al obtained only a 13% yield of the corresponding isothiocyanate.
The production of phenoxycarbonyl isothiocyanate is also taught by Babu; J. Heterocyclic Chem. 20, 1127, (1983). Thus, the prior art methods for preparing alkoxy and aryloxy isothiocyanates are ineffective in terms of yields and the formation of the undesirable thiocyanate isomer. Additionally, the use of organic solvents creates costly removal problems and poses serious air emission hazards.